Deletion of the Protein Kinase A/Protein Kinase G Target SMTNL1 Promotes an Exercise-adapted Phenotype in Vascular Smooth Muscle

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Takayuki Akimoto (Creator)

Thomas M. Coffman (Creator)

Michael B. Datto (Creator)

Carie Facemire (Creator)

Christopher N. Fortner (Creator)

Timothy P. Gavin (Creator)

Timothy A. J. Haystead (Creator)

Robert C. Hickner (Creator)

Ashley Kwon (Creator)

Ping Li (Creator)

Beata Lontay (Creator)

Everett McCook (Creator)

Sara E. Miller (Creator)

Ronald L. Neppl (Creator)

Jean-Claude Perriard (Creator)

Avril V. Somlyo (Creator)

Randy J. Thresher (Creator)

Shiliang Wang (Creator)

Anne A. Wooldridge (Creator)

Zhen Yan (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: In vivo protein kinases A and G (PKA and PKG) coordinately phosphorylate a broad range of substrates to mediate their various physiological effects. The functions of many of these substrates have yet to be defined genetically. Herein we show a role for smoothelin-like protein 1 (SMTNL1) a novel in vivo target of PKG/PKA in mediating vascular adaptations to exercise. Aortas from smtnl1-/- mice exhibited strikingly enhanced vasorelaxation before exercise similar in extent to that achieved after endurance training of wild-type littermates. Additionally con- tractile responses to alpha-adrenergic agonists were greatly attenuated. Immunological studies showed SMTNL1 is expressed in smooth muscle and type 2a striated muscle fibers. Consistent with a role in adaptations to exercise smtnl1-/- mice also exhibited increased type 2a fibers before training and better performance after forced endurance training compared smtnl1+/+ mice. Furthermore exercise was found to reduce expression of SMTNL1 particularly in female mice. In both muscle types SMTNL1 is phosphorylated at Ser-301 in response to adrenergic signals. In vitro SMTNL1 suppresses myosin phosphatase activity through a substrate-directed effect which is relieved by Ser- 301 phosphorylation. Our findings suggest roles for SMTNL1 in cGMP/cAMP-mediated adaptations to exercise through mechanisms involving direct modulation of contractile activity. Originally published Journal of Biological Chemistry Vol. 283 No. 17 Apr 2008

Additional Information

Publication

Other

Journal of Biological Chemistry. 283:17(April 2008) p. 11850-11859.

Language: English

Date: 2011

Keywords

exercise adapted phenotype, Protein kinases, vascular smooth muscle

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